Deferasirox Reduces Serum Ferritin and Labile Plasma Iron in RBC Transfusion-Dependent Patients With Myelodysplastic Syndrome

Purpose This 3-year, prospective, multicenter trial assessed the safety and efficacy of deferasirox in low-or intermediate-1-risk myelodysplastic syndrome (MDS). Patients and Methods Eligible patients had serum ferritin >= 1,000 mu g/L and had received >= 20 units of RBCs with ongoing transfusion requirements. The starting dose of deferasirox was 20 mg/kg/d, with dose escalation up to 40 mg/kg/d permitted. Results A total of 176 patients were enrolled, and 173 patients received therapy. Median serum ferritin decreased 23% in the 53% of patients who completed 12 months of treatment (n = 91), 36.7% in patients who completed 2 years (n = 49), and 36.5% in patients who completed 3 years (n = 33) despite continued transfusion requirement. Reduction in serum ferritin significantly correlated with ALT improvement (P < .001). Labile plasma iron (LPI) was measured quarterly during the first year of the study. Sixty-eight patients (39.3%) had elevated LPI at baseline. By week 13, LPI levels normalized in all patients with abnormal baseline level. Fifty-one (28%) of 173 patients experienced hematologic improvement by International Working Group 2006 criteria; of these, only seven patients received growth factors or MDS therapy. Over the 3-year study, 138 (79.8%) of 173 patients discontinued therapy, 43 patients (24.8%) because of adverse events or disease progression and 23 patients (13.2%) because of abnormal laboratory values. The most common drug-related adverse events were gastrointestinal disturbances and increased serum creatinine. There were 28 deaths, none of which were considered related to deferasirox. Conclusion Deferasirox reduces serum ferritin and LPI in transfusion-dependent patients with MDS. A subset of patients had an improvement in hematologic and hepatic parameters.